Social relationships have a significant effect on overall health, and the bereavement and grief associated with losing a close relationship is associated with increased rates of morbidity and mortality. The general j goal of this application is to begin deconstructing the mechanisms through which social relationships are beneficial to mental and physical health, especially in aging. The hypothesis to be examined suggests that oxytocin (OT) plays a central role in buffering against emotional and autonomic reactivity, including stress and anxiety which may have broad consequences for health in old age. To dissect the physiological j mechanisms that underie the connection between stress and sociality, we will use the prairie vole (Microtus j ochrogaster), an animal similar to humans (but unique among rodents) in its tendency to form selective, long-lasting social bonds. Prairie voles also have a human-like autonomic nervous system and produce high levels of OT, making them an ideal model for translational studies on the mechanisms underlying the connection between social relationships and health. The proposed integrative experiments will examine behavioral, neuroendocrine and autonomic changes: following social separation and isolation, as a function of the presence or absence of OT. Research has shown that OT promotes social affiliation and buffers against stressors. However, recent work has also shown that OT is heightened after a long period of separation from a familiar social partner. The experiments proposed herein will closely examine the function of this separation-induced rise in OT by administering exogenous OT, or by blocking the actions of endogenous OT with a selective antagonist. Comparisons between central and peripheral administrations will demonstrate where OT is acting to produce changes in the emotional and physiological reactivity to stressors. Clarifying the mechanisms through which- social separation and isolation lead to detrimental changes will ultimately result in more targeted therapeutic approaches that hold promise for both prevention and treatment of age-related disease. 1: The loss of close social relationships, especially in old age, is potentially one of the strongest risk factors for mental and physical decline, but its mechanisms remain largely unknown. This work seeks to understand: the underlying physiological mechanisms in order to guide both behavioral and pharmacological efforts to prevent disease and promote health in the elderly.